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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Afferent projections to the mediodorsal and anterior thalamic nuclei in the cat were studied by means of stereotaxic injection of neuronal tracers (horseradish peroxidase and fluorochromes). Acetylcholinesterase reaction was studied, as well as horseradish peroxidase and NADPH-diaphorase colocation in neuronal bodies which send and receive projections to and from the mediodorsal thalamic nucleus. Based on the connectivity and histochemistry findings, the possibility that prion agents responsible for fatal familial insomnia spread from the mediodorsal and anterior thalamic nuclei through a retrograde pathway is discussed. The possible pathophysiological implication of nitrergic systems in fatal familial insomnia is also considered.
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PMID:Afferent projections to the mediodorsal and anterior thalamic nuclei in the cat. Anatomical-clinical correlations. 966 6

Donepezil is an acetylcholinesterase inhibitor indicated for the symptomatic treatment of mild to moderate Alzheimer's disease. It is reported to have a relatively favourable side-effect profile. We report here on a pharmacovigilance study carried out post-marketing in England. An observational cohort study using the technique of Prescription-Event Monitoring was carried out. Some 1762 patients (mean age 72.9 years; 42% male) were followed up for 6 months minimum. The commonest adverse events were nausea, diarrhoea, malaise, dizziness and insomnia. Aggression, agitation and abnormal dreams were uncommonly associated with the drug. There were no cardiac rhythm disturbances or liver disorders causally associated. The commonest adverse drug reactions are already reported in the product information. Given the relatively small size of this cohort, the signals of abnormal dreams and psychiatric disturbance as possible adverse drug reactions need further investigation in carefully planned studies.
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PMID:Adverse effects associated with the use of donepezil in general practice in England. 1119 60

Exposure to organophosphates (OP) has been associated with sleep disorders such as insomnia and "excessive dreaming." The central mechanisms of these effects are not well understood. OPs inhibit acetylcholinesterase (AChE) activity, leading to a hyperactivity of the brain cholinergic systems that are involved in sleep regulation. We studied alterations in the EEG, behavioral states, motor activity and core temperature in rats orally administered with 10 or 40 mg/kg of the OP insecticide chlorpyrifos (CHP). Occipital EEG, motor activity and core temperature were recorded with telemetric transmitters. Behavioral sleep-wake states were visually scored. Both doses of CHP produced alterations of the EEG (decrease in power of sigma/beta and increase in slow theta and fast gamma bands) characteristic of arousal. EEG alterations were consistent with behavioral changes such as an increase in wakefulness and a decrease in sleep. Waking immobility was a prevalent behavior. We did not detect any overt signs of CHP toxicity, such as an abnormal posture or gait, suggesting that reduced locomotion can be a result of central effects of CHP (such as activation of cholinergic motor inhibitory system) rather than peripheral (such as an impairment of neuromuscular function). Changes in the EEG and behavior occurred independently of the decrease in core temperature. Increased wakefulness together with reduced motor activity after exposure to CHP seems to be a result of hyperactivity in brain cholinergic neuronal networks.
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PMID:EEG spectra, behavioral states and motor activity in rats exposed to acetylcholinesterase inhibitor chlorpyrifos. 1217 64

This article reviews the piperidine derivative, donepezil hydrochloride (E2020, Aricept), a reversible central acetylcholinesterase inhibitor currently approved for treatment of mild-to-moderate Alzheimer's disease. Donepezil is well absorbed orally, unaffected by food or by time of administration; it reaches therapeutic levels in doses of 5-10 mg/day and peak plasma concentrations are obtained 3-4 h after oral administration. A single bedtime dose is recommended due to the long elimination half-life of the drug (70 h). Donepezil does not cause liver toxicity or significant drug interactions and is relatively well-tolerated. Initial side effects include nausea, vomiting, diarrhoea, insomnia, muscle cramps, fatigue, anorexia and syncope. Caution is advised in patients with bradycardia. Long-term use of donepezil in AD has been found to delay nursing-home placement and to result in caregiver respite. Donepezil also slows deterioration of cognition and global function in patients with moderate-to-severe AD, with improvement of abnormal behaviours. In addition to AD, donepezil demonstrates significant improvement in cognition, global function and activities of daily living in comparison with placebo-treated patients with vascular dementia and has potential therapeutic benefit for other neurological conditions.
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PMID:Donepezil: a clinical review of current and emerging indications. 1468 Apr 45

Daytime sedation is a common and potentially dose-limiting side effect of the opiate analgesics. The psychostimulants, such as methylphenidate, are frequently prescribed to treat this problem, but their use may be limited by side effects, such as weight loss, anxiety, or insomnia, or tolerance to their antisedative effects. Medications which enhance intracerebral cholinergic activity may offer an alternative treatment approach, since functional deficits of acetylcholine may, in part, account for the sedative and mind-dulling effects of opiates. Preliminary studies with donepezil, a centrally acting acetylcholinesterase (AChE) inhibitor approved for use in Alzheimer's disease, have suggested at least short-term benefit in treating opiate-related sedation. In a retrospective study, we reviewed the results of donepezil treatment in 40 patients, 37 of whom had cancer, which in most cases was in an advanced stage. All patients were receiving chronic opiate treatment, and the majority were on a stable opiate dose in the 2 weeks preceding the initiation of donepezil. The average opiate dose was 844 mg in oral morphine equivalents. Seventy-three percent of the patients experienced moderate or greater improvement on the Clinical Global Improvement Scale. Evaluations on the Epworth Sleepiness Scale (ESS; 0-24), visual analog sleepiness scale (VAS; 0-100), and average pain levels (0-100), before and after donepezil treatment, were obtained on 19 patients. Prior to donepezil, ESS, VAS, and pain scores were 18.5, 76.3, and 47.4. After an average of 21 days of donepezil treatment, scores were 9.5 (P < 0.001), 39.5 (P < 0.001), and 36.6 (P = 0.07), respectively. The mean total duration of treatment for patients was 54.4 days, with most patients stopping donepezil due to progression to a terminal state. Patients were generally started on 5 mg/ day, but 17 patients required higher doses to achieve or maintain efficacy, the average treatment dose being 9.13 mg/day. We concluded from this study that centrally acting AChE inhibitors are promising agents in the treatment of sedation,and perhaps of other neuropsychological side effects associated with the use of opiate analgesics.
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PMID:Treatment of opiate-related sedation: utility of the cholinesterase inhibitors. 1535 44

Cholinesterase (ChE) inhibitors, which prevent the hydrolysis of acetylcholine, have been approved for the symptomatic treatment of Alzheimer's disease (AD) for over a decade. However, the first ChE inhibitors were associated with a high incidence of side-effects and general tolerability concerns, including hepatotoxicity. Side-effects associated with increased cholinergic activity, particularly in the gastrointestinal (GI) system, can prevent patients from achieving effective doses of drug. In addition, the advanced age and frail nature of patients with AD mean that poor tolerability is a serious concern. The potential for drug-drug interactions is also an important consideration, due to the high prevalence of comorbid disease in these patients. Data both from clinical trials and studies in routine clinical practice have shown that donepezil is associated with a low incidence of GI adverse events (AEs) that is comparable with placebo. Donepezil is a potent, selective inhibitor of acetylcholinesterase, and selective inhibition of central as opposed to peripheral ChEs might be expected to reduce the incidence of AEs, thus this may explain the lower incidence of cholinergic AEs observed following treatment with donepezil, compared with nonselective ChE inhibitors. There are no differences in cardiovascular AEs, including bradycardia, between placebo and donepezil groups in the clinical trials published to date, even in a very sick vascular dementia population with high rates of comorbidity and concomitant medication use. Data from single- and multiple-dose studies of donepezil in patients with hepatic impairment and with moderately to severely impaired renal function indicate that donepezil is safe and well tolerated in these groups. Furthermore, both in vitro and clinical studies have shown that donepezil is not associated with drug-drug interactions. The incidence of weight loss is very similar between donepezil- and placebo-treated patients. Although insomnia and other sleep disorders have been reported following administration of donepezil, lengthening the time period before increasing the dose of donepezil from 5 to 10 mg day(-1) or switching to morning dosing can reduce these events to the levels of placebo-treated patients. Over 770 million days of patient use and an extensive publication database demonstrate that donepezil has a good tolerability and safety profile.
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PMID:The safety and tolerability of donepezil in patients with Alzheimer's disease. 1549 17

Methyl parathion - MP (C[8]H[10rsqbNO[5rsqbPS) is a restricted-use pesticide that has been widely used as an agricultural insecticide. It belongs to the class of organophosphate chemicals characterized by their ability to inhibit acetylcholinesterase activity. The main route of human exposure is inhalation, but dermal contact and inadvertent ingestion can also be substantial. Populations that are susceptible to MP exposure primarily are applicators, manufacturers and individuals living near application and/or disposal sites. Exposure has also been reported as a result of illegal indoor application. MP related health effects include headaches, nausea, night-waking, diarrhea, difficulty breathing, excessive sweating and salivation, incoordination, and mental confusion. Other symptoms including behavior problems, motor skill problems and impairment of memory recall have also been reported. The primary targets of toxicity are the hematopoietic system (serum cholinesterase inhibition), the cardiovascular system (cardiovascular lesions, abnormalities in heart rate and increase in heart-to-body ratio), the reproductive system (placental morphology, fibrosis and hemorrhage, and inhibition of DNA synthesis in seminiferous tubules), and the nervous system (headache, muscle weakness, insomnia, dizziness, and impaired memory). MP is believed to not have any carcinogenic effects. In an attempt to update its toxicologic profile, we hereby provide a critical review of MP-related environmental and toxicologic effects, with a special emphasis on their potential implications for public health.
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PMID:Environmental toxicology and health effects associated with methyl parathion exposure--a scientific review. 1681 98

Donepezil is a reversible inhibitor of acetylcholinesterase. Its commonest adverse events are nausea, diarrhoea, malaise, dizziness, and insomnia. Symptomatic cardiac rhythm disturbances associated with the use of donepezil are extremely unusual. An 82 year old patient with Alzheimer's disease (AD) developed complete atrioventricular block and ventricular tachyarrhythmia 1 month after starting treatment with donepezil, and was admitted to the emergency department because of dizziness and syncope. Immediately after admission, a temporary ventricular pacing catheter was placed in the right ventricle. Rhythm was observed to return to a normal sinus rhythm on the fourth day after implantation. Treatment of AD with cholinesterase inhibitors carries a risk of cardiac disturbances. In addition to sinusal bradycardia, it may lead to such major dysrhythmias as complete atrioventricular block and ventricular tachyarrhythmia, as in our case. In this report, we describe symptomatic complete atrioventricular block and ventricular tachyarrhythmia associated with the use of donepezil.
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PMID:Complete atrioventricular block and ventricular tachyarrhythmia associated with donepezil. 1685 1

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory loss and cognitive impairment. It is the most common type of dementia in the ageing population due to a severe loss of cholinergic neurons in selected brain area. At present, acetylcholinesterase inhibitors (AChEI) are the first group of drugs approved by the FDA to treat mild to moderate Alzheimer's disease. Most of these drugs such as huperzine and galanthamine are originally isolated from plants. In this study, the AChE inhibitory activities from extracts of Chinese medicinal herbs that have traditionally been prescribed to treat insomnia and brain function disorders were examined in a 96-well plate assay based on Ellman's method. Both ethanol and aqueous extracts of 26 traditional Chinese medicinal herbs were tested. Inhibitory effects were expressed as the percentage of inhibition. For the herbal extracts that were shown to exert a significant inhibition, dose-dependent inhibitory assays were also performed. Ethanol and aqueous extracts of six herbs were found to have high AChE inhibitory activities in a dose-dependent manner. The IC(50) of these herbal extracts on inhibition of AChE are at around 5-85 microm/ml. The results of this study indicate that there is a great potential to search for novel usage of these medicinal herbs for the treatment of AD.
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PMID:Anti-acetylcholinesterase activities of traditional Chinese medicine for treating Alzheimer's disease. 1857 42

In Oriental medicine, roots of Polygala tenuifolia Willdenow have been known to be an important herb that exhibits sedative effects in insomnia, palpitation with anxiety, restlessness, and disorientation in humans. We previously reported that BT-11, extracted from those roots, improved scopolamine-induced amnesia in rats and inhibited acetylcholinesterase activities in vitro. Therefore, we proposed that BT-11 could remedy stress-induced memory deficits in rats. In this study, the stress-induced memory impairments in rats were significantly reversed almost to the control level by BT-11 treatment. To seek an active component of BT-11 that plays an important role in antipsychotic effects, we compared BT-11 with 3,4,5-trimethoxycinnamic acid (TMCA), which is a constituent of those root extracts. However, the effects of TMCA were less or were not consistent with those of BT-11 in some of tests. In particular, BT-11 reversed the stress-induced reduction of glucose utilization by [(18)fluorodeoxyglucose]FDG-PET and the levels of neural cell adhesion molecule (NCAM) in rat brains to the control levels, whereas TMCA did not. Therefore, BT-11 improved stress-induced memory impairments through increment of glucose utilization and total NCAM levels in rat brains. In conclusion, BT-11 may be strongly effective against stress-induced amnesia in rats, through the combined effects of TMCA and other active components of BT-11.
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PMID:BT-11 improves stress-induced memory impairments through increment of glucose utilization and total neural cell adhesion molecule levels in rat brains. 1871 49


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